Moxness, M., et al. (Ann. N. Y. Acad. Sci. USA 1005 (2003) 265-268) reported a radioligand binding assays for total and Ig classes of insulin antibodies (IAB). Test and control sera first were acidified to dissociate bound insulin, and charcoal was added to adsorb the serum insulin. After neutralization, the charcoal with bound insulin was removed from the serum by centrifugation. For each assay, insulin-extracted serum samples were incubated with radiolabeled insulin in the presence and absence of high levels of unlabeled insulin to determine nonspecific binding and total binding, respectively.
Patton, A., et al. (J. Immunol. Meth. 304 (2005) 189-195) reported a bridging ELISA that uses a covalently coupled high density antigen surface combined with an acid dissociation step to allow for antibody detection in the presence of antigen in human serum, i.e. without prior removal of excess antigen.
Lee, J. W., et al. (AAPS J. 13 (2011) 99-110) report that the predominant driver of bioanalysis in supporting drug development is the intended use of the data. Reliable methodologies for measurements of mAb and its target ligand (L) in circulation are crucial for the assessment of exposure-response relationships in support of efficacy and safety evaluations, and dose selection. Ligand-binding assays (LBA) are widely used for the analysis of protein biotherapeutics and target ligands (L) to support pharmacokinetics/pharmacodynamics (PK/PD) and safety assessments. For monoclonal antibody drugs (mAb), in particular, which non-covalently bind to L, multiple forms of mAb and L can exist in vivo, including free mAb, free L, and mono- and/or bivalent complexes of mAb and L. Given the complexity of the dynamic binding equilibrium occurring in the body after dosing and multiple sources of perturbation of the equilibrium during bioanalysis, it is clear that ex vivo quantification of the forms of interest (free, bound, or total mAb and L) may differ from the actual ones in vivo. LBA reagents and assay formats can be designed in principle to measure the total or free forms of mAb and L. However, confirmation of the forms being measured under the specified conditions can be technically challenging.
Kelly, M., et al. (AAPS J., 15 (2013) 646-658) report that one area that has been getting increasing attention recently is in the assessment of “free” and “total” analyte and the impact of the assay format on those assessments. The authors provide a critical review of available literature and prospectively explore methods to mitigate the potential impact of anti-drug antibody on PK assay measurement. Furthermore the methods for increasing drug tolerance in ADA (anti-drug antibody) assays could be re-purposed for assessing or increasing ADA tolerance in PK assays, usually with a preparatory step to break up the immune complex and extract the drug. It must be noted that implementation of such challenging manipulations would not be considered routine for late-stage clinical bioanalysis, but would provide valuable information early on in the investigative stage of method development to pharmacokinetics for their interpretation. Ultimately, any extraction process used to help quantitate drug would likely result in a “total” assessment.
Davis, R. A., et al. (J. Pharm. Biomed. Anal. 48 (2008) 897-901) reported a method for quantifying total (free plus bound) biomarker concentration in the presence of high levels of therapeutic MoAb using a single non-competing MoAb in a capture/acid elution format. This assay has the capability to accurately detect and quantitate circulating ng/ml biomarker levels in the presence of 200 μ/ml or more of therapeutic MoAb.
Salimi-Moosavi, H., et al. (J. Pharm. Biomed. Anal. 51 (2010) 1128-1133) reported alkaline and acid/guanidine treatment approaches to dissociate the protein binding and preferentially denature the ThA. The neutralized target proteins can be determined by ELISA. These methods provide reproducible measurements of total target protein without ThA interference. Serum samples, standards and QCs containing target protein and ThA were treated with alkaline buffer (pH>13) containing casein or acid/guanidine buffer (pH<1). Total target proteins for two different ThA systems were successfully measured and interferences were completely eliminated by the treatments. These methods were successfully applied to analysis in pre-clinical serum samples.
In US 2015/226758 methods and kits for detecting the presence of anti-drug antibodies in a sample, and more particularly to methods and kits for detecting anti-drug antibodies in the presence of a drug in the sample are reported.
In US 2012/269728 devices and methods for real time detection of target agents in a sample are reported. These devices utilize tracking technology and selective binding to allow the identification of one or more target agents in a sample, and preferably in a biological sample.
Li, J., et al. reported the detection of low-affinity anti-drug antibodies and improved drug tolerance in immunogenicity testing by Octet<(>R) biolayer interferometry (J. Pharm. Biomed. Anal. 54 (2011) 286-294).
Mikulskis, A., et al. reported about a solution ELISA as a platform of choice for development of robust, drug tolerant immunogenicity assays in support of drug development (J. Immunol. Meth. 365 (2010) 38-49).
Qiu, Z. J., et al., reported a novel homogeneous biotin-digoxigenin based assay for the detection of human anti-therapeutic antibodies in autoimmune serum (J. Immunol. Meth. 362 (2010) 101-111).
Zhong, Z. D., et al. reported the identification and inhibition of drug target interference in immunogenicity assays (J. Immunol. Meth. 355 (2010) 21-28).